rs142426153

Variant names:

• chr7-148409373-CTCTT-C
• rs142426153
• NM_014141.6:c.3716-10_3716-7delTTCT

Your query was ambiguous. Multiple possible variants found:

• chr7-148409373-CTCTT-C
• chr7-148409373-CTCTT-CTCTTTCTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014141.6(CNTNAP2):​c.3716-10_3716-7delTTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTNAP2 NM_014141.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 5 publications found

Genes affected

CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

CNTNAP2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, NO_KNOWN Submitted by: ClinGen
• cortical dysplasia-focal epilepsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

ENSG00000287636 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.3716-10_3716-7delTTCT		splice_region_variant, intron_variant	Intron 22 of 23	ENST00000361727.8	NP_054860.1
LOC105375554	XR_928094.2	n.210-14685_210-14682delAAGA		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.3716-17_3716-14delTCTT		intron_variant	Intron 22 of 23	1	NM_014141.6	ENSP00000354778.3

Frequencies

GnomAD3 genomes AF: 0.0000346 AC: 1 AN: 28930 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000787

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000478 AC: 4 AN: 837344 Hom.: 0 AF XY: 0.00000704 AC XY: 3 AN XY: 426146

African (AFR) AF: 0.00 AC: 0 AN: 17236

American (AMR) AF: 0.00 AC: 0 AN: 39404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19330

East Asian (EAS) AF: 0.00 AC: 0 AN: 33050

South Asian (SAS) AF: 0.0000178 AC: 1 AN: 56292

European-Finnish (FIN) AF: 0.0000313 AC: 1 AN: 31966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4262

European-Non Finnish (NFE) AF: 0.00000334 AC: 2 AN: 599146

Other (OTH) AF: 0.00 AC: 0 AN: 36658

GnomAD4 genome AF: 0.0000346 AC: 1 AN: 28930 Hom.: 0 Cov.: 0 AF XY: 0.0000695 AC XY: 1 AN XY: 14394

African (AFR) AF: 0.00 AC: 0 AN: 4860

American (AMR) AF: 0.00 AC: 0 AN: 5654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 984

East Asian (EAS) AF: 0.00 AC: 0 AN: 2010

South Asian (SAS) AF: 0.00 AC: 0 AN: 696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 108

European-Non Finnish (NFE) AF: 0.0000787 AC: 1 AN: 12702

Other (OTH) AF: 0.00 AC: 0 AN: 454

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142426153; hg19: chr7-148106465;